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Objectives: Treatment-emergent central sleep apnea (TECSA) is well established in continuous positive airway pressure therapy but was barely studied in mandibular advancement device (MAD) treatment. This study aims to evaluate the prevalence of TECSA in patients treated with a MAD and to determine its risk factors and clinical relevance., Materials and Methods: A total of 139 patients from the IRSR Pays de la Loire Sleep Cohort suffering from snores or obstructive sleep apnea syndrome (OSAS) and treated with a custom-made titratable MAD were included. Baseline and follow-up sleep recordings enabled identification of TECSA patients. Comparative analyses were carried out between TECSA and non-TECSA groups to identify potential risk factors. Clinical relevance of TECSA in both groups was assessed through baseline and follow-up Pichot's self-assessment questionnaire for depressive symptoms (QD2A), 36-item short form survey (SF-36) and Epworth Sleepiness Scale (ESS) scores., Results: According to the definition selected, a prevalence between 0 % and 5.04 % was found for TECSA in the present study. No statistical differences were found in terms of treatment characteristics, sleep architecture, demographic data or comorbid conditions, although there was a trend towards a higher prevalence of arterial hypertension in TECSA-1 than in non-TECSA group (42.9 % vs 25.4 % respectively, p = 0.379). Baseline ESS showed a trend towards a higher score in TECSA-1 patients compared to non-TECSA patients (13/24 vs 10/24 respectively, p = 0.074), with a high proportion of TECSA-1 patients suffering from excessive daytime sleepiness before initiation of treatment (85.7 %, vs 52.4 % in non-TECSA patients, p = 0.124). No statistical differences were found regarding delta Pichot's QD2A and ESS scores between baseline and follow-up although there was a trend towards higher ESS scores at follow-up in TECSA-1 group compared to non-TECSA patients. Median delta SF-36 score for the General health scale was significantly lower in TECSA-1 and there was a trend towards lower scores for Mental health category in TECSA-1 patients., Conclusions: TECSA is a rare phenomenon that can occur in patients treated with a MAD for an OSAS. Clinical, polysomnographic and treatment-related risk factors have yet to be reassessed in larger cohorts. These findings suggest probably poorer subjective clinical outcomes in terms of sleepiness and quality of life in patients with MAD-related TECSA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

A large proportion of genetic variations involved in complex diseases are rare and located within noncoding regions, making the interpretation of underlying biological mechanisms a daunting task. Although technical and methodological progress has been made to annotate the genome, current disease-rare-variant association tests incorporating such annotations suffer from two major limitations. First, they are generally restricted to case-control designs of unrelated individuals, which often require tens or hundreds of thousands of individuals to achieve sufficient power. Second, they were not evaluated with region-based annotations needed to interpret the causal regulatory mechanisms. In this work, we propose RetroFun-RVS, a new retrospective family-based score test, incorporating functional annotations. A critical feature of the proposed method is to aggregate genotypes to compare against rare variant-sharing expectations among affected family members. Through extensive simulations, we have demonstrated that RetroFun-RVS integrating networks based on 3D genome contacts as functional annotations reach greater power over the region-wide test, other strategies to include subregions and competing methods. Also, the proposed framework shows robustness to non-informative annotations, maintaining its power when causal variants are spread across regions. Asymptotic p-values are susceptible to Type I error inflation when the number of families with rare variants is small, and a bootstrap procedure is recommended in these instances. Application of RetroFun-RVS is illustrated on whole genome sequence in the Eastern Quebec Schizophrenia and Bipolar Disorder Kindred Study with networks constructed from 3D contacts and epigenetic data on neurons. In summary, the integration of functional annotations corresponding to regions or networks with transcriptional impacts in rare variant tests appears promising to highlight regulatory mechanisms involved in complex diseases., (© 2025 The Author(s). Genetic Epidemiology published by Wiley Periodicals LLC.)

Background and Objectives: Spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) due to acid ceramidase deficiency is a rare disorder, allelic with Farber disease, resulting from recessive ASAH1 variants. Patients present in early childhood with muscle weakness due to anterior horn degeneration and/or progressive drug-resistant myoclonic epilepsy. Death usually results from respiratory complications or status epilepticus during adolescence., Methods: We identified 9 patients with SMA-PME from 5 different families followed in neurology, rehabilitation, and genetics departments of university hospitals in France and the United States. During disease progression, motor functional scores were assessed for seven of them and C26-ceramide quantification on dried blood spots (DBSs) was performed for 4 of them. An in cell assay, measuring the degradation rate of ceramides in living skin fibroblasts, was also performed in 2 patients. Finally, a literature review was conducted., Results: Twelve years after the molecular characterization of SMA-PME, here we present the detailed history of 9 patients from 5 different families with 4 new ASAH1 variants. The prospective follow-up for 4 of them allows us to evaluate the relevance of functional scales and of C26-ceramide assay on DBS, as a biomarker. In addition, an in cell assay could provide a more reliable level of the residual ceramidase activity. Based on a comprehensive literature review, we provide a detailed description of the natural history of the 44 patients with SMA-PME diagnosed to date and show a genotype-phenotype correlation for the 2 main variants and the disease onset., Discussion: This study presents the detailed natural history of SMA-PME. Given the rarity of this disease and the current lack of a reliable biomarker for patient follow-up, this work may serve as a retrospective control group for future therapeutic trials., Competing Interests: Quantification of C26-ceramide on DBSs was carried out by Camille Moreau, Adrien Paquot, and Terence Beghyn from the biotechnology company APTEEUS, and funded by the patient organization ASAP for Children. The other authors have no conflicts of interest to declare. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/NG., (Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Objectives: To evaluate the effect at 3 months of an intensive cervical traction protocol on disability in people with cervical radiculopathy and compare with placebo traction., Design: The trial is national, multi-centre, randomised, placebo-controlled and single-blinded. It began in March 2024 and will end in September 2027. Participants are allocated to receive mechanical cervical traction or placebo mechanical cervical traction., Setting: Seven hospitals in France., Participants: We will include 206 individuals with cervical radiculopathy diagnosed 3 to 12 months previously, hospitalised to undergo mechanical traction. Main inclusion criteria: age ≥ 18 years, Neck Disability Index ≥ 15/50 points and presence of ≥ 3 of 4 diagnostic signs of cervical radiculopathy., Interventions: All participants undergo 2 × 30 min of traction per day for 5 consecutive days. For mechanical cervical traction, the maximum weight is ≤ 12 kg and for placebo traction ≤ 600g., Main Outcome Measures: The primary outcome is disability (Neck Disability Index), secondary outcomes include pain related outcomes, medication consumption, surgery and days off work., Results: This study will provide a robust evaluation of the mid-term effectiveness of mechanical traction on disability in chronic cervical radiculopathy. The results will demonstrate whether a simple technique involving a short, intensive protocol reduces the duration of disability and pain., Conclusions: The availability of robust evidence supporting or refuting the use of cervical traction as part of the management of cervical radiculopathy will enable optimisation of treatment. The results could lead to the drafting of evidence-based recommendations regarding the use of mechanical traction to treat cervical radiculopathy., Clinial Trial Registration Number: ClinicalTrials.gov (NCT05952167)., Competing Interests: Declarations. Ethics approval and consent to participate: Ethical approval was granted by: Comité de protection des personnes Sud-Méditerranée I, number 23.01774.000234. Verbal consent is collected from participants, in line with French regulations for category 2 interventional research. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Outcomes derived from digital health technologies (DHTs) are promising candidate markers for monitoring Parkinson's disease (PD) progression. They have the potential to represent a significant shift in clinical research and therapeutic development in PD. However, their ability to track disease progression is yet to be established. This systematic review aimed to identify digital biomarkers capable of tracking early PD progression (disease duration <5 years) by reviewing longitudinal studies (minimum follow-up of 6 months). We evaluated study design and quality, population features, reported DHTs and their performance to track progression. Of 1507 records screened, 15 studies were selected, published between 2009 and 2023, with the majority coming from the last 5 years. Of the 15, 11 were observational and four were interventional trials (follow-up range: 6-60 months). Twelve different DHTs were used (8 required active tests, 8 in-hospital use), capturing features related to motor function and daily activities, including five DHTs focused on gait/posture. Rating scales were used as comparators in all but one study. Three DHTs detected longitudinal changes when scales did not, with one study showing larger effect sizes for change over time of selected DHT features compared to rating scales. Four studies showed longitudinal correlations among DHT features and rating scales. Preliminary promising data suggest that DHT-derived outcomes may help reduce sample sizes in disease-modifying trials. There is a need to standardize study methodologies and facilitate data sharing to confirm these results and further validate the sensitivity of DHTs to track disease progression in PD. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Sphingosine-1-phosphate (S1P) is a signaling lysolipid critical to heart development, immunity, and hearing. Accordingly, mutations in the S1P transporter SPNS2 are associated with reduced white cell count and hearing defects. SPNS2 also exports the S1P-mimicking FTY720-P (Fingolimod) and thereby is central to the pharmacokinetics of this drug when treating multiple sclerosis. Here, we use a combination of cryo-electron microscopy, immunofluorescence, in vitro binding and in vivo S1P export assays, and molecular dynamics simulations to probe SPNS2's substrate binding and transport. These results reveal the transporter's binding mode to its native substrate S1P, the therapeutic FTY720-P, and the reported SPNS2-targeting inhibitor 33p. Further capturing an inward-facing apo state, our structures illuminate the protein's mechanism for exchange between inward-facing and outward-facing conformations. Finally, using these structural, localization, and S1P transport results, we identify how pathogenic mutations ablate the protein's export activity and thereby lead to hearing loss., Competing Interests: Competing interests: J.S., F.W., H.B., and A.E. are employees of Bayer AG. Y.N.C. and V.P. are employees of Nuvisan ICB GmbH. G.S.F is co-founder and owns shares of Solgate GmbH, and SLC-focused company. The remaining authors declare no competing interests., (© 2025. The Author(s).)

Continuous compensation for cerebral dopamine deficiency represents an ideal treatment for Parkinson's disease. Dopamine does not cross the digestive and blood-brain barriers and is rapidly oxidized. The new concept is the intracerebroventricular administration of anaerobic dopamine (A-dopamine) using an abdominal pump connected to a subcutaneous catheter implanted in the third ventricle, near the striatum. An open-label phase 1 study showed no serious adverse reactions induced by A-dopamine in 12 patients. A randomized, controlled, open-label, crossover phase 2 study of 1 month of A-dopamine versus 1 month of optimized oral antiparkinsonian therapy was conducted in 9 patients. The primary endpoint, a blinded assessment of the percentage over target (that is, time with dyskinesia or bradykinesia), recorded by home actimetry using a wristwatch, was significantly reduced on A-dopamine compared with that on oral treatment alone (P = 0.027), with a median within-patient difference of -10.4 (Hedge g = -0.62 (95% confidence interval: -1.43, -0.08)). Home diaries were also significantly improved. These initial data on the feasibility, safety and effects of this new device-assisted therapy suggest validation by a large randomized double-blind trial. ClinicalTrials.gov registration: NCT04332276 ., Competing Interests: Competing interests: D.D., C.M., J.C.D. and M.F. have an equity stake in InBrain Pharma. A.D. and M.F. are employees of InBrain Pharma. C.M. has received grants from the France Parkinson charity and honoraria from Orkyn, Apopharma and Boston Scientific for consultancy and lectures on Parkinson’s disease at symposia. C.M. is CMO of Feetme and holds stakes in InBrain Pharma and InVenis Biotherapies. P.O. is the director of the pharmaceutical department of the University Hospital of Lille and leads the research group on injectable forms and associated technologies. As such, P.O. has signed contracts with many pharmaceutical companies. All contracts are signed by delegations from the University of Lille or CHU Lille. There are no personal contracts. D.D. has received PHRC grants from the French Ministry of Health (PHRC and ANR), European grants (H2020 and Coen) and research funding from the ARSLA charity, France; Parkinson charity; Fondation Credit Agricole, and Fondation de France. He has served on advisory boards, served as a consultant and given lectures for pharmaceutical companies such as Abbvie, Alterity, Orkyn, Air Liquide, Elivie, Homeperf, Apopharma, Lundbeck, Everpharma, Medtronic, Boston Scientific, Everpharma, UCB Pharma, EISAI, Servier, PTC Therapeutics, Orion, AB Science, Alzprotect, Cajal Neuroscience and Cure Parkinson Trust. He holds stakes in InBrain Pharma and InVenis Biotherapies. G.T., N.R., C.B., D.L., N.C., B.P., F.M., B.G., K.D., L.C., A.S.R., D.D. and J.C.D. have nothing to declare., (© 2025. The Author(s).)

Dispensing of misoprostol and mifepristone by pharmacies and chemist shops for self-management of medication abortion (MA) fills a crucial gap in settings where abortion care by trained health professionals is not readily available. This promising service delivery pathway, endorsed by the World Health Organization (WHO), is hindered by concerns of poor-quality care. Simulated clients collected data on MA pill dispensing practices from 92 pharmacies and chemist shops in three Nigerian states and 127 pharmacies in an Indian state that we have anonymized. Guided by the WHO's abortion guideline, we measured process-related quality indicators such as medication use instructions, warning signs, and respectful treatment among other aspects. We aggregated indicators under three domains: technical competence, information given to clients, and client experience. Overall, 51% of facilities in the Nigerian states and 32% in the Indian state offered MA pills. Most dispensing facilities offered the misoprostol-only regimen in Nigeria (68%) and the combination regimen in the Indian state (83%). Among facilities offering MA pills, 26% in Nigeria and 78% in the Indian state provided correct instructions on route of pill administration. Accurate information on the appropriate interval between pill type in the combination regimen was low in Nigeria (27%) and the Indian state (14%). Excessive bleeding as a warning sign was discussed more frequently in the Indian (56%) versus Nigerian states (32%); other abnormal bleeding patterns were rarely mentioned. Aggregate technical competency scores were low at 18% in Nigeria and 34% in the Indian state, with highest scores for client experience at 90% and 91% respectively. Findings suggest that people using MA pills purchased from the retail market are not given accurate and adequate information for most effective self-use. If MA self-management remains outside regulatory boundaries, technical quality will remain sub-standard, imposing unnecessary costs to people, their health, and health systems., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Shankar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Dissipative environments are ubiquitous in nature, from microscopic swimmers in low-Reynolds-number fluids to macroscopic animals in frictional media. In this study, we consider a mathematical model of a slender elastic locomotor with an internal rhythmic neural pattern generator to examine various undulatory locomotion such as Caenorhabditis elegans swimming and crawling behaviours. By using local mechanical load as mechanosensory feedback, we have found that undulatory locomotion robustly emerges in different rheological media. This progressive behaviour is then characterized as a global attractor through dynamical systems analysis with a Poincaré section. Furthermore, by controlling the mechanosensation, we were able to design the dynamical systems to manoeuvre with progressive, reverse and turning motions as well as apparently random, complex behaviours, reminiscent of those experimentally observed in C. elegans . The mechanisms found in this study, together with our dynamical systems methodology, are useful for deciphering complex animal adaptive behaviours and designing robots capable of locomotion in a wide range of dissipative environments.

We described the case of a 33-year-old patient who presented to the emergency department with non-febrile jaundice associated with epigastric pain. He suffered from acute non-severe alcoholic hepatitis and cholestasis. Biochemical investigations highlighted a huge elevation of the alpha-1-globulins fraction with an unexpected peak in the alpha-1-globulins area in serum protein electrophoresis, a severe hypercholesterolemia without xanthelasmas nor cholesterolomas. Investigations revealed an abnormal lipoprotein, Lipoprotein X (LpX) that can be responsible for the hypercholesterolemia, but also interferes with biochemical tests like direct low-density lipoprotein cholesterol, albumin, and serum electrolytes assays. LpX is an abnormal lipoprotein, which can be present in patients with liver dysfunction, notably in cholestasis-related conditions where the metabolism of plasma lipoproteins is altered. Cholestasis prevents the normal formation of bile acids, leading to the formation of LpX, which is rich in phospholipids and unesterified cholesterol, but poor in esterified cholesterol, triglycerides and proteins. The accumulation of LpX can lead to severe hypercholesterolemia, but this remains uncommon and data regarding the pathophysiology and incidence of this disease is scarce. The laboratory investigation of patients with suspected Lpx can be challenging, due to the lack of available methods for measurement of LpX. In conclusion, LpX-induced hyperlipidemia must be identified to prevent interference in results for a number of biochemical tests, and additionally to improve patient care., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Reducing nigrostriatal iron overload reduces neuronal loss in Parkinson's disease (PD) models., Objective: Examine the safety and efficacy of deferiprone in reducing motor disability progression in dopaminergic-treated and treatment-naïve patients with early-stage PD., Methods: Two phase II, multicenter studies, SKY and EMBARK, enrolled patients diagnosed with early PD (<3 years from screening). In SKY, patients on stable dopaminergic therapy were randomized 1:1 to one of four dosage (or placebo-matching) cohorts (300, 600, 900, 1200 mg twice daily [BID]) for 9 months. EMBARK enrolled patients on stable dopaminergic therapy or treatment-naïve patients and received 15 mg/kg BID. For both studies, the primary outcome was the change from baseline to month 9 in motor examination score (Movement Disorder Society-Unified Parkinson's Disease Rating Scale [MDS-UPDRS] Part III). ClinicalTrials.gov: NCT02728843; ANZCTR: ACTRN12617001578392., Results: Overall, 140 patients were randomized in SKY (28 per cohort). Thirty-six patients enrolled in EMBARK (27 dopaminergic-treated; 9 treatment-naïve). In the SKY study, all doses showed the same worsening as the placebo group, with the exception of the 600 mg dose, which was associated with non-significant reductions in MDS-UPDRS Part III least-squares mean (LSM) between baseline and 9 months (-2-8 points versus placebo). In EMBARK, LSM (SE) changes from baseline in MDS-UPDRS Part III were nonsignificant (-1.6 [1.7]) and significant (8.3 [3.9]) for dopaminergic-treated and treatment-naïve patients, respectively, the latter indicating disease worsening. Adverse events possibly related to deferiprone were reported in 35.7%-88.9% across all deferiprone groups vs. 42.9% for placebo., Conclusions: SKY and EMBARK studies indicate that deferiprone combined with L-dopa does not provide significant motor function benefit, while the absence of L-dopa treatment worsens symptoms., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: DD has served on several scientific advisory boards for Air Liquide, Boston Scientific, Ever Pharma, Lundbeck, and Orkyn and has an equity stake in InBrain Pharma.OR has received honorarium for scientific advice and consultancy from AbbVie, Adamas, Acorda, Addex, Aguettant, Alkahest, AlzProtect, Apopharma, AstraZeneca, Bial, Biogen, Britannia, Buckwang, Cerevel, Clevexel, Irlab, Eli Lilly, Lundbeck, Neuroderm, ONO Pharma, Orion Pharma, Osmotica, Oxford Biomedica, Pfizer, Prexton Therapeutics, Sanofi, Servier, Sunovion, Théranexus, Takeda, Teva, UCB, Watermark Research, XenoPort, XO, Zambon and scientific grants from Agence Nationale de la Recherche (ANR), CHU de Toulouse, France-Parkinson, INSERM-DHOS Recherche Clinique Translationnelle, MJFox Foundation, Programme Hospitalier de Recherche Clinique, European Commission (FP7, H2020).WGM has received fees for editorial activities with Elsevier and consultancy fees from Lundbeck, Biohaven, Roche, Alterity, Servier, Inhibikase, Takeda, and Teva.CT has received nonfinancial support from Allergan and Merz.KE received funding from the German Parkinson Society, AbbVie, Acorda, Adamas, Addex, Apopharma, Benevolent, Bial, Biogen, Biotie, Impax, Kyowa, Novartis, Pfizer, Roche, and UCB; advisory board fees from Bial, Kyowa Kirim, Stadapharm, and Zambon; and speaker fees from AbbVie, Bial, Desitin, UCB, and Zambon.CC has received grants for research from Parkinson's UK, Edmond J. Safra Foundation, National Institute of Health and Care Research, and Cure Parkinson's; and personal fees from AbbVie, Abidetex, Bial, Britannia, EverPharma, Global, Kinetics, Kyowa Kirin, Lundbeck, MedScape, Mission Therapeutics, Orkyn, Scient, Pfizer, and UCB. CC is an Editorial Board member of this journal but was not involved in the peer-review process of this article nor had access to any information regarding its peer review.NP has received consultancy and speaker fees from 4D Pharma, AbbVie, Bial, Britannia, and Roche.OS has received grants from Wave Life Sciences and Roche, royalties from UpToDate, is on the Safety Monitoring Committee for Alexion, and served on the Scientific Advisory Board for AbbVie.LVK has served on advisory boards for AC Immune, Allergan/AbbVie, Ipsen, Right Brain Bio, and UCB and has received honoraria from Sun Pharma and Takeda.SD declares boards and congress with Medtronic, Orkyn, AbbVie, LVL, Homeperf, Elivie.TD has received personal fees for scientific expertise from AbbVie.AS has been a consultant for and has received consultant and speaker fees from Medtronic Inc., Boston Scientific, and St Jude Medical/Abbott.JCC has served on advisory boards for Air Liquide, Biogen, BrainEver, Denali, EverPharma, Prevail Therapeutic, and UCB and has received grants for research from Sanofi.GD has received personal compensation for scientific advisory boards and funding for travel and/or speaker honoraria from Biogen, Bristol Myers Squibb, Merck Serono, Novartis, Sanofi Genzyme, Teva Pharmaceuticals; and research grants (paid to institution) from Biogen, Merck Serono, Novartis, and Sanofi Genzyme.NTT, CF, and FT are employees of Chiesi Canada Corporation.CM has received grants from the France Parkinson charity and various honoraria from pharmaceutical companies for consultancy and lectures on Parkinson disease and symposia, such as Aguettant, AbbVie, Medtronic, and Novartis.The remaining authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Freezing of gait (FoG) is among the most disabling gait disorders of Parkinson's disease. The full understanding of its mechanisms requires a network study approach. So far, FoG was mainly studied using magnetic resonance imaging, and especially using the resting state functional sequence, which does not completely reflect the brain actual modifications., Objective: This study aims to investigate metabolic networks using position emission tomography (PET) imaging. Exploration after a rest or gait session combined with a delayed tracer's uptake are assumed to reflect the actual metabolism modifications., Methods: Twenty-six patients in the off-drug state underwent two PET imaging sessions using [ 18 F]- fluorodeoxyglucose, the first after 30 min of rest (rest condition) and the second after 30 min of real gait (gait condition). Twelve patients presented real FoG during cerebral glucose uptake. Brain connectivity matrices were measured for each group and condition, and then compared., Results: In the rest condition, the freezing group showed globally reduced metabolic connectivity between brain regions compared to the non-freezing group. During gait, enhanced connectivity was observed in the cerebellum, cerebello-cortical loops and parieto-frontal regions, with high recruitment of the visual cortex in the freezing group. However, connectivity inside cerebellar networks remained lower in the freezing group than in the non-freezing group, while occipito-frontal connectivity was higher in the freezing group., Conclusions: Studying real freezing of gait in a vertical position emphasized the role of the visual cortex and cerebellum in gait problems., Competing Interests: Declaration of conflicting interestsProfessor Caroline Moreau is an Editorial Board member of this journal, but was not involved in the peer-review process of this article nor had access to any information regarding its peer review. The remaining authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Competing Interests: The authors report no financial relationships with commercial interests.

Purpose: This study explores whether economic instability or food insecurity moderates the changes in emotional abuse and neglect over time., Methods: We used data from the Global Early Adolescent Study, a longitudinal study among adolescents ages 13-18 years (10-14 during pre-COVID-19 round) from poor urban communities in China (n = 387), the Democratic Republic of Congo (DRC) (n = 285), Indonesia (n = 400), and Malawi (n = 320). Data were collected before (2017 to March 2020) and during the pandemic (June to November 2020). Generalized estimating equations, using inverse probability weights evaluated changes in emotional abuse and neglect pre- and during COVID-19 and tested whether these changes varied by economic instability and food insecurity experiences during COVID-19., Results: Pre-COVID-19, emotional abuse ranged from 37.2% in DRC to 65.3% in Indonesia, and emotional neglect from 10.9% in DRC to 50.3% in Indonesia. The odds of emotional neglect increased in all sites during COVID-19 except Indonesia (adjusted odds ratio (aOR) ranging from 1.7 in China to 4.1 in Malawi). In Indonesia, odds of abuse and neglect decreased significantly during COVID-19 (aOR ranging from 0.4 to 0.7); however, emotional abuse and/or neglect declines was less pronounced for those who experienced economic instability and/or food insecurity. In Malawi, adolescents who experienced food insecurity had a significant increase in odds of emotional neglect during COVID-19., Discussion: The COVID-19 pandemic exacerbated emotional neglect and emotional abuse among adolescents living in low- and middle-income countries, although this effect varies by place and population. In Malawi and Indonesia, adolescents who experienced economic instability and/or food insecurity had more unfavorable outcomes during COVID-19, highlighting the importance of social programs correcting inequities during pandemics., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: This study aims to assess anxiety trends over the COVID-19 pandemic and evaluate how pandemic-related adversities modify trajectories among underprivileged adolescents from two distinct settings., Methods: Data came from the Shanghai, China and Kinshasa, Democratic Republic of the Congo sites of the Global Early Adolescent Study. Data were collected three times over approximately two years: prior to the pandemic (T1) and during the pandemic (T2, T3). Analyses included adolescents (aged 10-16) with complete information on generalized anxiety disorder (GAD) across all time points (Shanghai N = 548; Kinshasa N = 334). Weighted Generalized Estimating Equations assessed anxiety at T2 and T3 relative to T1. Effect modification analyses were used to investigate if COVID-19-related adversities modified anxiety trajectories., Results: Six months into the pandemic, 15.3% (Shanghai) and 4.1% (Kinshasa) of adolescents reported having moderate-to-severe GAD. Adjusted Generalized Estimating Equation models did not suggest increases in GAD during the pandemic across both sites. However, female adolescents from Shanghai experienced increased anxiety (adjusted odds ratio [aOR]: 2.27, 95% confidence interval: 1.30-3.99) half a year into the pandemic. The trend was not sustained. COVID-related adversities did not modify anxiety trajectories in Kinshasa. In Shanghai, one year into the pandemic, we observed decreased odds of GAD among all (aOR: 0.31, 0.17-0.58) and female adolescents (aOR: 0.25, 0.08-0.75) without pandemic-associated negative household experiences., Discussion: The COVID-19 pandemic differentially affected adolescent anxiety by time, place, and gender. Future research should examine the roles of social context and resilience to better understand adolescents' mental distress and to guide health-promoting programs and policies for young people., (Copyright © 2024 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Study Question: Does the prevalence of 12-month infertility in Burkina Faso, Côte d'Ivoire, Kenya, and Uganda differ between women trying to conceive and the broader population of women exposed to unprotected sex, and how are prevalence estimates affected by model assumptions and adjustments?, Summary Answer: Estimates of 12-month infertility among tryers ranged from 8% in Burkina Faso to 30% in Côte d'Ivoire, increasing substantially among a larger population of women exposed to unprotected intercourse., What Is Known Already: While having a child is a fundamental human experience, the extent to which women and couples experience infertility is a neglected area of research, particularly in sub-Saharan Africa. Existing estimates of infertility in this region vary widely from 2% to 32%, however, potential impacts of variability in study populations and model assumptions have not been well-examined., Study Design, Size, Duration: We used cross-sectional nationally representative survey data from Burkina Faso, Côte d'Ivoire, Kenya, and Uganda. We employed a multi-stage cluster random sampling design with probability proportional to the size selection of clusters within each country to produce representative samples of women aged 15-49. Samples ranged from 3864 in Côte d'Ivoire to 9489 in Kenya., Participants/materials, Setting, Methods: We created two analytic samples in each country-tryers and a broader sample of women exposed to unprotected sex-exploring differences in population characteristics and estimating the period prevalence of 12-month infertility using the current duration (CD) approach. We also examined the impact of several model assumptions within each of the two analytic samples, including adjustments for recent injectable contraceptive use, unrecognized pregnancy, infertility treatment, underreported contraceptive use, and sexual activity., Main Results and the Role of Chance: Employing the CD approach among tryers produced an overall 12-month infertility prevalence of 7.9% (95% CI 6.6-12.7) in Burkina Faso, 29.6% (95% CI 15.3-100.0) in Côte d'Ivoire, 24.5% (95% CI 16.5-34.6) in Kenya, and 14.7% (95% CI 8.1-22.4) in Uganda. Results among women exposed to unprotected intercourse indicated much higher levels of infertility, ranging from 22.4% (95% CI 18.6-30.8) in Uganda to 63.7% (95% CI 48.8-87.9) in Côte d'Ivoire. Sensitivity analyses suggest infertility estimates are particularly sensitive to adjustments around pregnancy recognition timing and sexual activity, with little impact of adjustments for recent injectable contraceptive use, infertility treatment, and underreporting of traditional and coital dependent contraceptive use., Limitations, Reasons for Caution: There was substantial digit preference in responses at 12 months, particularly among the tryers, which could introduce bias. Data quality concerns in the reproductive calendar may impact the accuracy of the CD approach among the broader sample of women exposed to unprotected sex, particularly with regard to underreported contraceptive use, induced and spontaneous abortions, and unrecognized pregnancies. Lastly, we lacked information on postpartum amenorrhea or abstinence., Wider Implications of the Findings: Understanding the inconsistencies in definition and analytic approach and their implications for infertility estimation is important for reliably monitoring population-level infertility trends, identifying factors influencing infertility, improving prevention programs, and ensuring access to quality treatment and services., Study Funding/competing Interest(s): This study was supported by grants from the Bill & Melinda Gates Foundation (INV009639) and the National Institute of Child Health and Human Development (K01HD107172). The funders were not involved in the study design, analyses, manuscript writing, or the decision to publish. The authors have no conflicts of interest to declare., Trial Registration Number: N/A., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The administration of adjuvant imatinib during 3 years is indicated after resection of primary localized GIST at high risk of recurrence, but many patients relapse afterwards., Methods: IMADGIST (NCT02260505) was a multicenter, open-label, randomized phase III study evaluating the maintenance of imatinib for 3 more years (6-year arm) compared with interruption (3-year arm) from the day of randomization, conducted in the French Sarcoma Group. The primary endpoint was intent-to-treat disease-free survival. Secondary endpoints included overall survival, time to imatinib resistance, response after imatinib reintroduction at relapse, and safety., Results: From 24 December 2014 to 4 April 2023, 136 patients aged ≥18 years, Eastern Cooperative Oncology Group performance status ≤2, with a localized gastrointestinal stromal tumor with an R0 or R1 surgery, and a risk of tumor recurrence ≥35% according to National Comprehensive Cancer Network (NCCN) risk classification were randomized in 14 centers. Sixty-five patients were randomized to the 3-year arm versus 71 to the 6-year arm. There were 68 males and females. Primary sites were gastric and small bowel in 60 (44%) and 64 (47%) patients, respectively. Respectively, 52 (38%) and 71 (52%) patients had a risk of relapse of 35%-70% and >70%. With a median follow-up of 55 months (interquartile range 46-59 months) after randomization, disease-free survival was significantly superior in the 6-year arm [hazard ratio: 0.40 (0.20-0.69), P = 0.0008]. Time to imatinib resistance, survival, adverse events, and quality of life were not different in the two arms., Conclusions: Three additional years of adjuvant imatinib reduces the risk of relapse in patients who have received 3 years of adjuvant imatinib with an acceptable tolerance., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: This study examines the experiences of pregnant/parenting adolescents and young women during the first two years of the coronavirus disease 2019 (COVID-19) pandemic., Methods: This explanatory sequential mixed-methods study leverages quantitative data collected among a cohort of adolescents and young people aged 15-22 years in three Kenyan counties; Nairobi, Kisumu, and Kilifi at three time points (2020, 2021, 2022), and two rounds of qualitative interviews in the same settings conducted in 2020 and 2022., Results: Among 2337 (2020), 1438 (2021), and 1669 (2022) respondents, pregnant/parenting adolescents and youth comprised 140 (6%), 101 (7%), and 83 (5%) individuals, respectively. Across the three time points, the experience of depressive symptoms was similar between pregnant/parenting adolescents and those not pregnant/parenting. Pregnancy and parenting was associated with twice the odds of skipping health services (adjusted odds ratio [aOR] 2.18, 95% confidence interval [CI] 1.43-3.35), in 2020, and 85% higher odds (aOR 1.85, 95% CI 1.14-3.02) in 2021, and 90% higher odds of skipping meals (aOR 1.90, 95% CI 1.19-3.03) in 2022. Qualitative findings indicated experiences of psychological distress, food insecurity, and inadequate access to health care services among pregnant/parenting young people during the pandemic., Discussion: The pandemic increased pre-existing challenges associated with adolescent and young people's health, predisposing young pregnant/parenting women to greater adversity than their nonpregnant/parenting counterparts. Targeted and responsive approaches during emergencies and crises such as social protection, food security, and mental health programs for this group of vulnerable people are required and need to be integrated into disaster response plans., (Copyright © 2024 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

In response to the current challenge in genetic studies to make new associations, we advocate for a shift toward leveraging population fine-scale structure. Our exploration brings to light distinct fine-structure within populations having undergone a founder effect such as the Ashkenazi Jews and the population of the Quebec' province. We leverage the fine-scale population structure to explore its impact on the frequency of rare variants. Notably, we observed an 8-fold increase in frequency for a variant associated with the Usher syndrome in one Quebec subpopulation. Our study underscores that smaller cohorts with greater genetic similarity demonstrate an important increase in rare variant frequencies, offering a promising avenue for new genetic variants' discovery., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Gagnon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease with diverse clinical phenotypes, prompting the development of new diagnostic criteria known as the MDS-PSP classification. However, little is known about the prognostic value of this classification in order to better stratify patients for the clinical trials., Objective: To assess the impact of the different clinical phenotypes according to the MDS-PSP classification on prognosis using the clinical milestones of death, severe dysphagia, institutionalization, and need for walking aid., Methods: A prospective cohort of 205 PSP patients from Lille University Hospital was analyzed retrospectively. Patients were classified into different MSD-PSP phenotypes according to their clinical presentation after 3 years of follow-up. The milestones of death, severe dysphagia, institutionalization, and need for walking aid were recorded, and a survival analysis was performed to describe the prognosis of each disease presentation., Results: Median survival time was 6.4 (interquartile range (IQR): 4.8-8.6) years and mean diagnostic delay from symptom onset was 38.1 ± 22.5 months. PSP Richardson Syndrome (PSP-RS) had a poorer survival rate and a higher occurrence of severe dysphagia and need for walking aid compared to PSP variants such as PSP Parkinsonism (PSP-P), PSP postural instability without ocular motor dysfunction (PSP-PI), and other rare phenotypes., Conclusions: PSP-RS has a less favorable prognosis compared to PSP variants stratified according to the MDS-PSP classification. This classification could assist in selecting patients for clinical trials and help design outcomes that account for the disease heterogeneity., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Luc Defebvre served on the Scientific Advisory Board for Abbvie and has received honoraria from pharmaceutical companies for consultancy and lectures including Abbvie, Novartis, Aguettant, and Orkyn.Stéphanie Bombois received honoraria from Biogen for a symposium (2021) and from Esai for a lecture (2020), and is an investigator without personal fees in therapeutical trials for Alzheimer's disease from Biogen, Roche, Eisai, Eli Lilly, Janssen, Johnson & Johnson, Alector, NovoNordisk, Genentech, AB science, and Novartis​.David Devos has led four investigator-driven studies funded by academic grants from France from the French Ministry of Health and Research and the European Commission Horizon 2020 PHC13 2014–2015 (N° 633190), involving deferiprone, provided free of charge by ApoPharma Inc. and Chiesi Canada Corp. (FAIRPARK-I, FAIRPARK-II and SAFE-FAIR ALS-I, FAIR-ALS-II). He has served on advisory boards, served as a consultant and given lectures for pharmaceutical companies such as Orkyn, Abbvie, Medtronic, and Boston Scientific.Caroline Moreau has received grants from the France Parkinson & Vaincre Parkinson charities, and French ANR. She has received various honoraria from pharmaceutical companies for consultancy and lectures on Parkinson's disease at symposia, including Orkyn, Elivie, Abbvie, and Boston Scientific. She is an Editorial Board member of this journal, but was not involved in the peer-review process of this article nor had access to any information regarding its peer review.All other authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Acyl-CoA Oxidase-1 (ACOX1) deficiency (MIM 264470) is an autosomal recessive disease characterized by impairments in the desaturation of acyl-CoAs to 2-trans-enoyl-CoAs, which is the first step in the catalysis of the β-oxidative breakdown of very long chain fatty acids (VLCFA) occuring in peroxisomes. The deleterious accumulation of VLCFA in several organs, including the brain, is a key biochemical feature of this disease which has devastating neurological consequences. ACOX1 deficiency is ultra-rare; as such, few studies have been conducted to determine the leading causes of symptoms or uncover new therapeutics. When confronted with one such case, we decided to bring drug discovery tools to the patient's bedside in an attempt to identify a cure. A skin biopsy was performed on a young patient with ACOX1 deficiency, following which screening technologies and mass spectrometry analysis techniques were applied to design a cellular assay that enabled the direct measurement of the effect of small molecules on the patient's primary fibroblasts. This approach is particularly well adapted to inherited metabolic disorders such as ACOX1 deficiency. Through the evaluation of a proprietary library of repurposable drugs, we found that the anthelmintic drug niclosamide led to a significant reduction in VLCFA in vitro. This drug was subsequently administered to the patient for more than six years. This study outlines the screening and drug selection processes. Additionally, we present our comprehensive clinical and biochemical findings that aided in understanding the patient's natural history and analysis of the progression of the patient's symptoms throughout the treatment period. Although the patient's overall lifespan was extended compared to the average age at death in severe early onset cases of ACOX1 deficiency, we did not observe any definitive evidence of clinical or biochemical improvement during niclosamide treatment. Nonetheless, our study shows a good safety profile of long-term niclosamide administration in a child with a rare neurodegenerative disease, and illustrates the potential of individualized therapeutic strategies in the management of inherited metabolic disorders, which could benefit both patients and the broader scientific and medical communities., Competing Interests: Declaration of competing interest Terence Beghyn is Apteeus co-founder and chief executive officer. Camille Moreau and Adrien Paquot were members of the Apteeus operational team. Apteeus is a French biotechnology company. Part of the project described in this article was funded by Apteeus. Apteeus, Terence Beghyn, Camille Moreau and Adrien Paquot declare that they have no link with Bayer, which discovered niclosamide, or with several companies that currently market the drug. Apteeus, Terence Beghyn, Camille Moreau and Adrien Paquot received no funding from these companies., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The study focus is the valorization of banana agriculture by products by the extraction and derivatization of cellulose and its incorporation in formulations to produce superabsorbent materials endowed with high water absorption performances. The extracted cellulose (BP) was subjected to a controlled oxidation by sodium periodate to convert it to cellulose dialdehyde (DAC) with controlled aldehyde content. The cellulosic materials were incorporated into a suspension containing acrylic acid (AA) and itaconic acid (IA) to produce composite hybrid hydrogels (SA-BP/SA-DAC) by radical chain polymerization in water, using N,N-methylene-bis-acrylamide (MBA) as a cross-linking agent and potassium persulfate (KPS) as an initiator. The prepared materials were characterized using techniques such as Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and rheological analysis. Additionally, the absorption and re-swelling capacities of the superabsorbent composites (SAPs) were assessed through kinetic studies in water and NaCl solution. Notably, dialdehyde cellulose (DAC), due to its low crystallinity index, hydrophilicity (attributed to aldehyde and hemiacetal functions), and high polarity, holds promise for enhancing the swelling and water retention capacity of the hydrogel. A water absorption capacity as high as 1240±60 g.g-1 was obtained for SA-DAC with a DAC content of 5 %wt. Additionally, the reusability of the SAPs was evidenced., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Empowerment research has largely focused on adult women with little focus on younger adolescents. Additionally, despite recognition that empowerment is a process, few studies have longitudinally explored its development., Methods: We used secondary data from four waves of the Global Early Adolescent Study to explore trajectories in the development of three domains of agency (i.e. the internal processes composing empowerment) - Freedom of Movement, Voice, and Decision-Making - for 1188 boys and 1153 girls in Kinshasa, Democratic Republic of Congo. Respondents were age 10-14 at enrollment and followed through age 14-18. We created scales for each domain and conducted gender- and age-stratified latent growth curve modeling with random effects, comparing age 10-14 to age 15-18, accounting for clustering within individuals over waves. We examined the role of puberty within each domain in the analysis of age 10-14., Results: Scores across all domains increased with age for boys and girls, with the exception of Voice amongst boys 10-14. Rates of change varied by age group and gender; for boys, scores increased at a faster rate for older boys relative to younger boys for Freedom of Movement (ß (10-14) : 3.98 versus ß (15-18) : 6.12) and Voice (ß (10-14) : .50 versus ß (15-18) : 2.54). Relative to younger girls, scores amongst older girls increased at a faster rate for Freedom of Movement (ß (10-14) : 1.76 versus ß (15-18) : 3.72) and a slower rate for Decision-Making (ß (10-14) : 6.41 versus ß (15-18) : 2.80). Puberty was associated with significant increases in scores across all domains for both genders, with the exception of Decision-Making for girls., Interpretation: Young people develop/acquire different forms of agency at different stages of adolescence and development is not uniform across forms. Gender inequalities in agency amplify at puberty, signaling the need to intervene at or before this critical stage of development., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Linnea A Zimmerman reports financial support was provided by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Legume plants can acquire mineral nitrogen (N) either through their roots or via a symbiotic interaction with N-fixing rhizobia bacteria housed in root nodules. To identify shoot-to-root systemic signals acting in Medicago truncatula plants at N deficit or N satiety, plants were grown in a split-root experimental design in which either high or low N was provided to half of the root system, allowing the analysis of systemic pathways independently of any local N response. Among the plant hormone families analyzed, the cytokinin trans-zeatin accumulated in plants at N satiety. Cytokinin application by petiole feeding led to inhibition of both root growth and nodulation. In addition, an exhaustive analysis of miRNAs revealed that miR2111 accumulates systemically under N deficit in both shoots and non-treated distant roots, whereas a miRNA related to inorganic phosphate (Pi) acquisition, miR399, accumulates in plants grown under N satiety. These two accumulation patterns are dependent on Compact Root Architecture 2 (CRA2), a receptor required for C-terminally Encoded Peptide (CEP) signaling. Constitutive ectopic expression of miR399 reduced nodule numbers and root biomass depending on Pi availability, suggesting that the miR399-dependent Pi-acquisition regulatory module controlled by N availability affects the development of the whole legume plant root system., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Knowledge of the conditions under which abortion is legal is important so that people can advocate for their right to abortion care. Yet minimal research has explored the association between women's knowledge of abortion legality and the induced abortion care they receive, particularly using population-based survey data., Methods: Using national survey data collected by Performance Monitoring for Action (PMA) in Côte d'Ivoire and Ghana, we aimed to compare the prevalence of accurate knowledge of abortion legality, factors associated with knowledge of the law, and the association between knowledge of abortion legality and the source of women's induced abortion care in these two settings. We ran bivariate and multivariable logistic regressions to assess the relationships of interest., Results: We found that awareness and knowledge of the abortion law were low in both Côte d'Ivoire and Ghana. In Cote d'Ivoire, women who were older, more educated, and with past abortion experience were more likely to be aware of the law. In Ghana, knowledge of the law did not vary significantly by demographic characteristics. However, in Ghana, knowledge of the law was correlated with women's use of the formal healthcare system for abortion care, with greater use of clinical sources in rural areas., Conclusions: It is possible that for populations with reduced access to abortion services, such as those in rural areas, knowledge of the law is advantageous for those seeking facility-based abortion care, particularly in settings where abortion is legal for a range of indications. Interventions seeking to improve access to facility-based abortion care in settings where abortion is legal on various grounds should incorporate education on the legal grounds for abortion., (© 2024. The Author(s).)

Background: Abortion has been legal for multiple indications in Ghana since 1985, and efforts have been made to expand the availability of safe abortion care in the years since. However clandestine, and potentially unsafe, abortions remain common, suggesting numerous barriers to access persist; one possible barrier is poor knowledge of the abortion law among those working in health facilities. Our study aimed to identify levels of legal knowledge among health facility staff across Ghana., Methods: Data for this paper are drawn from a nationally representative cross-sectional health facility survey conducted in 2018; our analytic sample includes 340 facilities that provide induced abortion and/or postabortion care (PAC). The survey collected data on provision of abortion and PAC, as well as knowledge of abortion legality and recommendations for reducing unsafe abortion. We used descriptive statistics to examine levels of knowledge and recommendations, and logistic regression to assess associations with individual and facility characteristics., Findings: Comprehensive knowledge of the legal indications for abortion was low among health facility staff; just 6% identified all legal indications, and the majority (83%) underestimated the number of conditions under which abortion is legal. Knowledge was higher for more restrictive indications, such as a woman's life being at risk, which was identified by 72% of respondents, than more broadly interpretable indications, such as mental health, identified by 29%. Respondents in facilities providing both induced abortion and PAC had better knowledge of several legal indications than those in facilities providing PAC only., Conclusions: Health facility staff have significant gaps in their knowledge of abortion legality. Knowledge of the law among this population is highly important for ensuring that abortion care is made available to the fullest extent of the law. Efforts are needed to improve knowledge of the law among providers and facility staff, particularly for indications with broad interpretability., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sheehy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Lytic polysaccharide monooxygenase (LPMO)-catalyzed oxidative processes play a major role in natural biomass conversion. Despite their oxidative cleavage at the surface of polysaccharides, understanding of their mode of action, and the impact of structural patterns of the cellulose fiber on LPMO activity is still not fully understood. In this work, we investigated the action of two different LPMOs from Podospora anserina on celluloses showing different structural patterns. For this purpose, we prepared cellulose II and cellulose III allomorphs from cellulose I cotton linters, as well as amorphous cellulose. LPMO action was monitored in terms of surface morphology, molar mass changes and monosaccharide profile. Both PaLPMO9E and PaLPMO9H were active on the different cellulose allomorphs (I, II and III), and on amorphous cellulose (PASC) whereas they displayed a different behavior, with a higher molar mass decrease observed for cellulose I. Overall, the pretreatment with LPMO enzymes clearly increased the accessibility of all types of cellulose, which was quantified by the higher carboxylate content after carboxymethylation reaction on LPMO-pretreated celluloses. This work gives more insight into the action of LPMOs as a tool for deconstructing lignocellulosic biomass to obtain new bio-based building blocks., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jean-Guy Berrin reports financial support was provided by Carnot 3BCar Institute. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Many predicted that COVID-19 would have a substantial impact on the sexual and reproductive health (SRH) trajectories of adolescents in sub-Saharan Africa. The lack of longitudinal data with information collected before and into the pandemic has limited investigation into this topic., Methods: We performed a secondary analysis using nationally representative longitudinal data from Kenya and Burkina Faso, collected at three time points (pre-COVID-19 in late 2019, and during COVID-19 in 2020 and 2021), to determine the extent to which SRH outcomes and behaviors, including pregnancy, contraceptive use, partnership status, and sexual activity, changed during the pandemic among adolescent women., Results: Among adolescents aged 15-19 years (Kenya n = 1,893, Burkina Faso n = 1,422), there was a reduction in both partnership and pregnancy in 2021 as compared to pre-COVID 2019. Contraception use significantly increased between 2019 and 2021 in Kenya only (adjusted odds ratio [aOR]: 1.42, 95% confidence interval [CI] 1.03-1.97). COVID-19-related household income loss was associated with a decline in sexual activity among unmarried Kenyan girls (aOR: 0.47, 95% CI 0.25-0.87) and lower odds of pregnancy in Burkina Faso (aOR: 0.13, 95% CI 0.02-0.91). We did not find a relationship between COVID-19 measures and initiation of partnership or marriage in either setting., Discussion: Contrary to expectations, our results suggest that COVID-19 did not have a consistent or sustaining impact on adolescent SRH and behaviors in Burkina Faso and Kenya. Further research is needed to assess the longer-term implications of the pandemic on adolescent social and health outcomes., (Copyright © 2024 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Study Question: What is the nature of women's care-seeking for difficulties conceiving in sub-Saharan Africa (SSA), including the correlates of seeking biomedical infertility care at a health facility?, Summary Answer: Care-seeking for difficulties getting pregnant was low, much of which involved traditional or religious sources of care, with evidence of sociodemographic disparities in receipt of biomedical care., What Is Known Already: Nearly all research on infertility care-seeking patterns in SSA is limited to clinic-based studies among the minority of people in these settings who obtain facility-based services. In the absence of population-based data on infertility care-seeking, we are unable to determine the demand for services and disparities in the use of more effective biomedical sources of care., Study Design, Size, Duration: We used cross-sectional, population-based data from the Performance Monitoring for Action (PMA) female survey in eight geographies in SSA, including nationally representative data from Burkina Faso, Côte d'Ivoire, Kenya, and Uganda and regionally representative data from two provinces in the Democratic Republic of the Congo (DRC) (Kinshasa and Kongo Central) and two states in Nigeria (Kano and Lagos). We employed a multi-stage cluster random sampling design with probability proportional to size selection of clusters within each geography to produce representative samples of women aged 15-49. Samples ranged from 1144 in Kano, Nigeria, to 9489 in Kenya. PMA collected these data between November 2021 and December 2022., Participants/materials, Setting, Methods: We restricted the sample to women who had ever had sex, with analytic samples ranging from 854 in Kano to 8,059 in Kenya, then conducted descriptive and bivariable analyses to examine characteristics of those who sought care for difficulties getting pregnant. Among those who reported seeking care, we conducted bivariable and multivariable logistic regression analyses to determine factors associated with receipt of biomedical services from a health facility. All analyses were conducted separately by geography., Main Results and the Role of Chance: Our study found low levels of care-seeking for difficulties getting pregnant among sexually active women in eight geographies in SSA, ranging from 3.7% (Kenya) to 15.3% (Côte d'Ivoire). Of this, 51.8% (Burkina Faso) to 86.7% (Kinshasa) involved receipt of biomedical services in health facilities. While many factors were consistently associated with infertility care-seeking from any source across geographies, factors associated with receipt of biomedical care specifically were less pronounced. This may be a result of the highly limited sources of infertility services in SSA; thus, even privileged groups may struggle to obtain effective treatment for difficulties getting pregnant. However, we did observe disparities in biomedical care-seeking in our bivariable results in several geographies, with the wealthiest women, those with more education, and those residing in urban areas generally more likely to have sought biomedical care for difficulties getting pregnant., Limitations, Reasons for Caution: Our data lacked details on the nature of the services received and outcomes, and we do not have information on reasons why women chose the sources they did. Small samples of women who sought care limited our power to detect significant differences in care-seeking by women's characteristics in several geographies., Wider Implications of the Findings: Infertility and access to appropriate treatment are issues of reproductive health and human rights. While our results do not indicate to what extent use of non-biomedical sources of care is driven by preferences, cost, or lack of accessible services, it is clear from our results and existing literature that more needs to be done to ensure access to affordable, quality, cost-effective infertility services in SSA., Study Funding/competing Interest(s): This study was supported by grants from the Bill & Melinda Gates Foundation (INV009639) and the National Institute of Child Health and Human Development (K01HD107172). The funders were not involved in the study design, analyses, manuscript writing, or the decision to publish. The authors have no conflicts of interest to declare., Trial Registration Number: N/A., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The evolution of animals and their gut symbionts is a complex phenomenon, obscured by lability and diversity. In social organisms, transmission of symbionts among relatives may yield systems with more stable associations. Here, we study the history of a social insect symbiosis involving cephalotine ants and their extracellular gut bacteria, which come predominantly from host-specialized lineages. We perform multi-locus phylogenetics for symbionts from nine bacterial orders, and map prior amplicon sequence data to lineage-assigned symbiont genomes, studying distributions of rigorously defined symbionts across 20 host species. Based on monophyly and additional hypothesis testing, we estimate that these specialized gut bacteria belong to 18 distinct lineages, of which 15 have been successfully isolated and cultured. Several symbiont lineages showed evidence for domestication events that occurred later in cephalotine evolutionary history, and only one lineage was ubiquitously detected in all 20 host species and 48 colonies sampled with amplicon 16S rRNA sequencing. We found evidence for phylogenetically constrained distributions in four symbionts, suggesting historical or genetic impacts on community composition. Two lineages showed evidence for frequent intra-lineage co-infections, highlighting the potential for niche divergence after initial domestication. Nearly all symbionts showed evidence for occasional host switching, but four may, more often, co-diversify with their hosts. Through our further assessment of symbiont localization and genomic functional profiles, we demonstrate distinct niches for symbionts with shared evolutionary histories, prompting further questions on the forces underlying the evolution of hosts and their gut microbiomes., (© 2024 John Wiley & Sons Ltd.)

Staphylococcus aureus ( S. aureus ) is an opportunistic infectious pathogen, which causes a high mortality rate during bloodstream infections. The early detection of virulent strains in patients' blood samples is of medical interest for rapid diagnosis. The main virulent factors identified in patient isolates include leukocidins that bind to specific membrane receptors and lyse immune cells and erythrocytes. Duffy antigen receptor for chemokines (DARC) on the surface of specific cells is a main target of leukocidins such as gamma-hemolysin AB (HlgAB) and leukocidin ED (LukED). Among them, HlgAB is a conserved and critical leukocidin that binds to DARC and forms pores on the cell membranes, leading to cell lysis. Current methods are based on ELISA or bacterial culture, which takes hours to days. For detecting HlgAB with faster response and higher sensitivity, we developed a biosensor that combines single-walled carbon nanotube field effect transistors (swCNT-FETs) with immobilized DARC receptors as biosensing elements. DARC was purified from a bacterial expression system and successfully reconstituted into nanodiscs that preserve binding capability for HlgAB. Dynamic light scattering (DLS) and scanning electron microscopy (SEM) showed an increase of the DARC-containing nanodisc size in the presence of HlgAB, indicating the formation of HlgAB prepore or pore complexes. We demonstrate that this sensor can specifically detect the leukocidins HlgA and HlgAB in a quantitative manner within the dynamic range of 1 fM to 100 pM with an LOD of 0.122 fM and an LOQ of 0.441 fM. The sensor was challenged with human serum spiked with HlgAB as simulated clinical samples. After dilution for decreasing nonspecific binding, it selectively detected the toxin with a similar detection range and apparent dissociation constant as in the buffer. This biosensor was demonstrated with remarkable sensitivity to detect HlgAB rapidly and has the potential as a tool for fundamental research and clinical applications, although this sensor cannot differentiate between HlgAB and LukED as both have the same receptor.

Background: The development of noninvasive markers to assess mucosal healing in ulcerative colitis (UC) is essential in the treat-to-target era. The aim of this study was to evaluate the performance of intestinal ultrasound (IUS), fecal calprotectin (FC), and their combination to assess mucosal healing in UC patients., Methods: All consecutive patients between January 2021 and September 2022 with UC who underwent a complete colonoscopy and IUS and/or an FC test within 4 weeks were included in a prospective cohort. Bowel wall thickness (BWT) and the color Doppler signal (CDS) were assessed for each segment. Endoscopic mucosal healing was defined by a Mayo score of 0 to 1., Results: A total of 61 patients were included, of whom 79% showed endoscopic healing (26 Mayo 0 and 11 Mayo 1). Among the patients, 16 (27.6%) of 58 had a BWT <3 mm, and 41 (70.7%) of 58 had no CDS. The sensitivity, specificity, positive predictive value, and negative predictive value of a BWT <3 mm to predict endoscopic mucosal healing were 37%, 77%, 72%, and 44%, respectively. The association of FC <150 µg/g, a BWT <3 mm, and a CDS = 0 increased the specificity and positive predictive value (sensitivity 33%, specificity 94%, positive predictive value 89%, negative predictive value 48%). The combination of a normal IUS, no rectal bleeding, and an FC <172 µg/g identified all patients with mucosal healing., Conclusion: The combination of IUS and FC is effective in identifying mucosal healing in UC. Noninvasive evaluation of mucosal healing is possible for most UC patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Discriminatory gender norms can intersect and interact with other dimensions of discrimination-such as age, race, ethnicity, disability, education status, and sexual orientation-to shape individuals' experiences and impact their health and wellbeing. This interaction is referred to as intersectionality. Although the theory has been in circulation since the late 1980s, only recently has it gained traction in low-income and middle-income settings, and it has yet to fully penetrate global research on adolescence. The social and structural intersectional drivers of adolescent health and wellbeing, particularly during early adolescence (age 10-14 years), are poorly understood. The evidence base for designing effective interventions for this formative period of life is therefore relatively small. In this Review, we examine how gender intersects with other forms of disadvantage in the early stages of adolescence. Analysing data from hybrid observation-intervention longitudinal studies with young adolescents in 16 countries, our aim is to inform the health and wellbeing of girls and boys from a range of social contexts, including in conflict settings. Adolescents' perceptions about gender norms vary by context, depend on individual opinion, and are shaped by socioecological drivers of gender inequalities in health. Shifting those perceptions is therefore challenging. We argue for the importance of applying an intersectionality lens to improve health and wellbeing outcomes for young adolescents and conclude with five practical recommendations for programme design and research., Competing Interests: Declaration of interests PB is a paid staff member of WHO. All other authors declare no competing interests., (Copyright © 2024 World Health Organization. Published by Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Existing estimates of adolescent sexual and reproductive health (ASRH) behaviors may be a gross undercount given the sensitivity of this behavior in Indian culture. The objective of this study was to estimate ASRH behaviors in Rajasthan, India using direct questions and the best friend approach that seeks to reduce social desirability bias., Methods: We used population-based data of adolescents aged 15-19 in Rajasthan collected between September and December 2022. Data include whether the respondent and her closest female friend ever had a partner, ever had sex, ever used contraception, and were currently using contraception. We estimated respondent and best friend ASRH outcomes separately, overall and among unmarried adolescents for whom we anticipate social desirability bias is greatest., Results: The best friend approach performed well, with method assumptions largely met even before adjustments. Respondent and best friend estimates were similar among all adolescents except for current contraceptive use, which was higher for friends (though not significantly so). However, we observed large differences in ASRH behaviors between unmarried respondents and friends, with a significantly higher percentage of friends who ever had a partner (4.3% respondents, 11.6% friends), and a slightly higher percentage who ever had sex (2.4%, 3.8%) and who were currently using contraception (17.0%, 19.7% among those in need of contraception)., Conclusions: We observed potential benefits of using the best friend methodology in estimating premarital sexual activity, but further work is needed to refine social network-based measures of sensitive adolescent behaviors in larger study samples to better understand ASRH needs., (© 2024. The Author(s).)

Background: NMF are currently poorly evaluated in therapeutic decisions. A quantification of their severity would facilitate their integration. The objective of this study was to validate an autoquestionnaire evaluating the severity of non-motor fluctuations (NMF) in Parkinson's disease (PD)., Methods: Patients with PD were included in presurgical situation for deep brain stimulation of subthalamic nuclei. They participated in the PREDISTIM cohort (a study evaluating the predictive factors for therapeutic response of subthalamic stimulation in PD) in 17 centres in France. Our questionnaire, resulting from previous phases of development, included 11 non-motor symptoms (NMS). Their severity ranged from 0 to 10 and was assessed in OFF and then ON-Dopa to study their fluctuations., Results: 310 patients were included, of whom 98.8% had NMS and 98.0% had NMF. Each NMS was significantly improved by L-Dopa (decrease in severity score ranging from 43.1% to 69.9%). Fatigue was the most frequent and most severe NMS. NMS were considered more bothersome than motor symptoms by 37.5% of patients in OFF-Dopa and 34.9% in ON-Dopa., Conclusions: This is the first questionnaire allowing a real-time quantification of the severity of NMS and their fluctuation with levodopa. It was able to confirm and measure the effect of L-dopa and show differences according to the patients and the NMS. It differs from other questionnaires by its measurement at a precise moment of the severity of the NMS, allowing its use during pretherapeutic assessments.Our questionnaire has been validated to measure the severity of NMF. It will be able to quantify the non-motor effect of anti-parkinsonian treatments and could facilitate the integration of NMF in therapeutic decisions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Reproductive coercion (RC) is any intentional behavior that interferes with another's reproductive decision-making or pregnancy outcome. This study aims to qualitatively examine RC experiences and perceptions among women and men in Ethiopia, Nigeria (Kano and Anambra States), and Uganda. This is a secondary analysis utilizing qualitative data from the Women's and Girls' Empowerment in Sexual and Reproductive Health study. Across sites, focus group discussions (38 groups; n=320 participants) and in-depth interviews (n=120) were conducted, recorded, and transcribed. Transcripts were loaded into Atlas.ti, and quotes describing experiences of reproductive control or abuse were coded as "reproductive coercion." RC quotes were input into a matrix for thematic analysis. Emergent RC themes included indirect reproductive pressures, direct family planning interference, concurrent experiences of violence, and responses to RC. Indirect reproductive pressures included tactics to both promote and prevent pregnancy, while direct interference centered on pregnancy promotion. Women who were not compliant with their partners' reproductive demands were often subjected to violence from multiple actors (i.e., parents, in-laws, community members) in addition to their partners. Despite concurrent forms of violence, women across sites resisted RC by using contraceptives covertly, choosing to abort, or leaving their abusive partnerships. Women and men across sites indicated that men were highly influential in fertility. RC behaviors were a mechanism of control over desired reproductive outcomes, which were often rooted in perceptions of childbearing as social status. Findings indicate a need for more nuanced community interventions targeting social norms, as well as improved RC screening and response within health services., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Apis mellifera was used as a model species for ecotoxicological testing. In the present study, we tested the effects of acetone (0.1% in feed), a solvent commonly used to dissolve pesticides, on bees exposed at different developmental stages (larval and/or adult). Moreover, we explored the potential effect of in vitro larval rearing, a commonly used technique for accurately monitoring worker exposure at the larval stage, by combining acetone exposure and treatment conditions (in vitro larval rearing vs. in vivo larval rearing). We then analyzed the life-history traits of the experimental bees using radio frequency identification technology over three sessions (May, June, and August) to assess the potential seasonal dependence of the solvent effects. Our results highlight the substantial influence of in vitro larval rearing on the life cycle of bees, with a 47.7% decrease in life span, a decrease of 0.9 days in the age at first exit, an increase of 57.3% in the loss rate at first exit, and a decrease of 40.6% in foraging tenure. We did not observe any effect of exposure to acetone at the larval stage on the capacities of bees reared in vitro. Conversely, acetone exposure at the adult stage reduced the bee life span by 21.8% to 60%, decreased the age at first exit by 1.12 to 4.34 days, and reduced the foraging tenure by 30% to 37.7%. Interestingly, we found a significant effect of season on acetone exposure, suggesting that interference with the life-history traits of honey bees is dependent on season. These findings suggest improved integration of long-term monitoring for assessing sublethal responses in bees following exposure to chemicals during both the larval and adult stages. Environ Toxicol Chem 2024;43:1320-1331. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC., (© 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.)

The development of fully biobased hydrogels obtained by simple routes and in the absence of toxic or environmentally harmful reagents is a major challenge in meeting new societal demands. In this work, we discuss the development of hydrogels made from cellulose nanocrystals (CNCs) and xyloglucan (XG), two non-toxic, renewable, and biobased components. We present three strategies to fine-tune the functional properties. The first one consists in varying the XG/CNC ratio that leads to the modulation of the mechanical properties of hydrogels as well as a better comprehension of the gel mechanism formation. The second relies on tuning the XG chains' interaction by enzymatic modification to achieve thermoresponsive systems. Finally, the third one is based on the increase in the hydrogel solid content by osmotic concentration. The high-solid-content gels were found to have very high mechanical properties and self-healing properties that can be used for molding materials. Overall, these approaches are a case study of potential modifications and properties offered by biobased nanocolloidal hydrogels.

Background and Objectives: The impact of subthalamic deep-brain stimulation (STN-DBS) on motor asymmetry and its influence on both motor and non-motor outcomes remain unclear. The present study aims at assessing the role of STN-DBS on motor asymmetry and how its modulation translates into benefits in motor function, activities of daily living (ADLs) and quality of life (QoL)., Methods: Postoperative motor asymmetry has been assessed on the multicentric, prospective Predictive Factors and Subthalamic Stimulation in Parkinson's Disease cohort. Asymmetry was evaluated at both baseline (pre-DBS) and 1 year after STN-DBS. A patient was considered asymmetric when the right-to-left MDS-UPDRS part III difference was ≥ 5. In parallel, analyses have been carried out using the absolute right-to-left difference. The proportion of asymmetric patients at baseline was compared to that in the post-surgery evaluation across different medication/stimulation conditions., Results: 537 PD patients have been included. The proportion of asymmetric patients was significantly reduced after both STN-DBS and medication administration (asymmetric patients: 50% in pre-DBS MedOFF, 35% in MedOFF/StimON, 26% in MedON/StimOFF, and 12% in MedON/StimON state). Older patients at surgery and with higher baseline UPDRS II scores were significantly less likely to benefit from STN-DBS at the level of motor asymmetry. No significant correlation between motor asymmetry and ADLs (UPDRS II) or overall QoL (PDQ-39) score was observed. Asymmetric patients had significantly higher mobility, communication, and daily living PDQ-39 sub-scores., Conclusions: Both STN-DBS and levodopa lead to a reduction in motor asymmetry. Motor symmetry is associated with improvements in certain QoL sub-scores., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Previous studies in the ambulatory care setting have shown inconsistent results in regard to, or with respect to pharmacist telephonic transitions of care (TOC) encounters and reduction in 30-day readmission rates. No studies that have been completed within an accountable care organization (ACO) evaluating the impact of telephonic TOC encounters performed by a pharmacist have been identified. The objective of this study was to analyze the impact of clinical pharmacy telephonic TOC encounters on readmission rates within a primary care-based ACO. In this retrospective chart review, data for those who had a pharmacist telephonic TOC encounter and those who had an attempt were collected. The primary outcome of this study was all-cause 30-day readmission rate. Secondary outcomes included 30-day readmission rate for targeted disease states, time to readmission, and readmission reason the same as previous discharge reason. For subjects who received a telephonic TOC encounter, pharmacist intervention type and provider acceptance of intervention(s) were described. For the final analysis, 154 encounters were included, 83 encounters in the telephonic TOC encounter group, and 71 did not receive a telephonic TOC encounter. The 30-day readmission rates were similar among those who received a telephonic TOC encounter and those who did not: the difference was not significant (15.7% vs. 28.2%; P = 0.059). There was also no statistical difference in the secondary outcomes. Even so, the results of this study suggest that performing a pharmacist telephonic TOC encounter in a primary care-based ACO setting has the potential to reduce 30-day readmission rates and further research appears to be warranted in this important area of practice.

The main objective of this study was to use flash boiling atomization as a new method to inject suspensions with high solid content into the high-power plasma flow. The water-based suspension was prepared with submicron titanium oxide particles with an average size of 500 nm. The investigated solid concentrations were 20, 40, 55 and 70 wt%. Two plasma torches operated at 33, 70 and 110 kW were used to investigate the effect of increasing power on the deposited microstructure and deposition efficiency. At low torch power, the deposition efficiency decreased with increasing solid concentration, and deposits with a high number of unmelted particles were obtained with 70 wt% suspensions. At high torch power, the deposition efficiency increased with increasing solid concentration, and dense deposits were obtained with 70 wt% suspensions. XRD analysis was performed on all deposits to determine the distribution of rutile and anatase phases. The percentage of the anatase phase varied from 35.7% to 66.9%, depending on the power input and solid concentration.

Thalamic dysfunction has been implicated in multiple psychiatric disorders. We sought to study the mechanisms by which abnormalities emerge in the context of the 22q11.2 microdeletion, which confers significant genetic risk for psychiatric disorders. We investigated early stages of human thalamus development using human pluripotent stem cell-derived organoids and show that the 22q11.2 microdeletion underlies widespread transcriptional dysregulation associated with psychiatric disorders in thalamic neurons and glia, including elevated expression of FOXP2. Using an organoid co-culture model, we demonstrate that the 22q11.2 microdeletion mediates an overgrowth of thalamic axons in a FOXP2-dependent manner. Finally, we identify ROBO2 as a candidate molecular mediator of the effects of FOXP2 overexpression on thalamic axon overgrowth. Together, our study suggests that early steps in thalamic development are dysregulated in a model of genetic risk for schizophrenia and contribute to neural phenotypes in 22q11.2 deletion syndrome., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Pressurized cells with strong walls make up the hydrostatic skeleton of plants. Assembly and expansion of such stressed walls depend on a family of secreted RAPID ALKALINIZATION FACTOR (RALF) peptides, which bind both a membrane receptor complex and wall-localized LEUCINE-RICH REPEAT EXTENSIN (LRXs) in a mutually exclusive way. Here we show that, in root hairs, the RALF22 peptide has a dual structural and signalling role in cell expansion. Together with LRX1, it directs the compaction of charged pectin polymers at the root hair tip into periodic circumferential rings. Free RALF22 induces the formation of a complex with LORELEI-LIKE-GPI-ANCHORED PROTEIN 1 and FERONIA, triggering adaptive cellular responses. These findings show how a peptide simultaneously functions as a structural component organizing cell wall architecture and as a feedback signalling molecule that regulates this process depending on its interaction partners. This mechanism may also underlie wall assembly and expansion in other plant cell types., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Little is known about the process of seeking information related to abortion care options among women in the Democratic Republic of Congo (DRC). Understanding how women obtain information can help identify opportunities for intervention to increase awareness and use of safe pregnancy termination options. Using qualitative data collected from women in Kinshasa, DRC who reported having an abortion in the last 10 years, this study aims to determine how women navigate obtaining information about their options for abortion and the role of their social network in their information-seeking processes. Data for this analysis come from a mixed-method study of abortion in Kinshasa conducted from December 2021 to April 2022. Fifty-two qualitative interviews followed a structured interview guide, including open-ended questions and probes, developed by a multidisciplinary team of researchers in Kinshasa and the United States. Inductive thematic analysis was conducted using Atlas.ti, and a thematic analysis matrix was used to describe the major themes and subthemes. Thematic analysis revealed two main themes with nested subthemes. The first and most salient theme highlighted the highly selective and narrow information search process women engaged in, involving no others or very few individuals (e.g., partners, women in one's community, or providers) that the pregnant woman chose strategically. The second theme revealed the heterogeneous and often stigmatizing nature of these interactions, including attempts at deterrence from many sources and information of varying completeness and accuracy. While the recent liberalization of the abortion law in the DRC is essential to improve access to safe abortion, public health gains will not materialize unless they are accompanied by community-level actions to raise awareness about the legality and availability of safe abortions services, including medication abortion pills for safe self-managed abortion., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ngondo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Despite significant progress in cancer imaging and treatment over the years, early diagnosis and metastasis detection remain a challenge. Molecular magnetic resonance imaging (MRI), with its high resolution, can be well adapted to fulfill this need, requiring the design of contrast agents which target specific tumor biomarkers. Netrin-1 is an extracellular protein overexpressed in metastatic breast cancer and implicated in tumor progression and the appearance of metastasis. This study focuses on the design and preclinical evaluation of a novel Netrin-1-specific peptide-based MRI probe, GdDOTA-KKTHDAVR (Gd-K), to visualize metastatic breast cancer. The targeting peptide sequence was identified based on the X-ray structure of the complex between Netrin-1 and its transmembrane receptor DCC. Molecular docking simulations support the probe design. In vitro studies evidenced submicromolar affinity of Gd-K for Netrin-1 ( K D = 0.29 μM) and good MRI efficacy (proton relaxivity, r 1 at 9.4 T, 37 °C). -1 s -1 at 9.4 T, 37 °C). In vivo MRI studies in a murine model of triple-negative metastatic breast cancer revealed successful tumor visualization at earlier stages of tumor development (smaller tumor volume). Excellent signal enhancement, 120% at 2 min and 70% up to 35 min post injection, was achieved (0.2 mmol/kg injected dose), representing a reasonable imaging time window and a superior contrast enhancement in the tumor as compared to Dotarem injection.

Objective: To determine and compare the concentration of gentamicin in the lower airways and serum of healthy spontaneously breathing dogs after nebulization with 5% undiluted gentamicin during 3 versus 10 minutes., Animals: 10 healthy experimental Beagles., Methods: This was a prospective crossover study. A standardized bronchoalveolar lavage (BAL) procedure was performed in each dog after 1 week of administration of each of 2 different gentamicin nebulization protocols separated by a 1-week washout period. The 2 protocols consisted of nebulization of 5% undiluted gentamicin (50 mg/mL) twice daily either during 10 minutes per session (± 95 mg; 10-minute protocol) or 3 minutes per session (± 28 mg; 3-minute protocol). BAL fluid (BALF) was obtained under general anesthesia using a bronchoscope within 15 minutes after administration of the last nebulization. Blood was collected within 5 minutes after BALF collection. BALF and serum gentamicin concentrations were determined by particle-enhanced turbidimetric inhibition immunoassay. Concentrations between protocols were compared using a paired t test., Results: Both BALF and serum gentamicin concentrations were higher after the 10-minute protocol compared with the 3-minute protocol (mean ± SD: 2.41 ± 0.87 mg/L vs 1.25 ± 0.31 mg/L, P = .001; and 1.02 ± 0.59 mg/L vs 0.31 ± 0.24 mg/L, P < .0001 in BALF and serum, respectively), while the BALF-to-serum ratio did not differ between the protocols (3.75 [1.37 to 5.75] (median [IQR]) in the 3-minute protocol vs 2.48 [2.02 to 2.67] in the 10-minute protocol; P = .754)., Clinical Relevance: A 3-minute nebulization of gentamicin seems to achieve sufficient concentrations of gentamicin in the BALF to have good efficacy against aminoglycoside-sensitive bacteria while remaining below the toxic range values in blood.